A comparison of the effect of intranasal desmopressin and intramuscular hyoscine N-butyl bromide combination with intramuscular hyoscine N-butyl bromide alone in acute renal colic

BACKGROUND: Patients with acute renal colic usually require im mediate diagnosis and treatment. In this clinical t ri l analgesic effect of hyoscine N-butyl bromide and de smopressin combination in comparison with hyoscine N-butyl bromide alone in patients with acute renal colic in duced by urinary stones was assessed. METHODS: The study included 114 patients randomly allocated in two groups (A and B). Patients in group A recei ved 20 mg intramuscular hyoscine N-butyl bromide at adm ission time and patients in group B received 20 μg of intranasal desmopressin in combination with 20 mg intramuscula r hyoscine N-butyl bromide. A visual analogue scale (VAS; a 10cm horizontal scale ranging from "zero or no pain" to "10 or unbearable pain") was hired to assess the pati nts' pain severity at baseline, 30 and 60 minutes after the t reatments. RESULTS: On admission, the pain level was similar in both g roups (group A: 8.95 ± 0.11 and group B: 8.95 ± 0.1 2). In group A, the mean of pain level showed a decrease a fter 30 minutes (group A: 7.26 ± 0.25 and group B: 5.95 ± 0.28) but further decreasing did not occur; however in gr oup B, the pain consistently decreased and the mean after 60 minutes was significantly decreased (group A: 6.80 ± 0.31 a nd group B: 3.71 ± 0.31). No side effects were dete ct d in this study. CONCLUSIONS: The combination of hyoscine N-butyl bromide and des mopressin is more effective than hyoscine Nbutyl bromide alone in patients with renal colic. F urther studies are recommended to validate these fi ndings and compare the different doses of desmopressin.

cute renal colic is one of the most agonizingly painful events of a person's life.Most active emergency wards treat at least a patient with acute renal colic per day.Patients with acute renal colic are often seen and evaluated by emergency physicians at the beginning.Immediate initial treatment besides proper diagnosis and consultations are among the duties of the emergency physicians. 1,2-desamino-8-arginine vasopressin (desmopressin) is a vasopressin analogue with a potent antidiuretic activity and less pressor ef-fects in comparison with vasopressin.][5] According to the previous studies approximately 50 percent of patients who have been treated with intranasal desmopressin had complete relief/reduction of their acute renal colic pain. 1,3The usefulness of hyoscine Nbutylbromide in the treatment of renal colic is not confirmed yet.[6] A Intranasal desmopressin may be a reasonable treatment for patients with acute renal colic however further studies are necessary to establish its place. 7,8To our knowledge, there is no publication on the effect of intranasal desmopressin and intramuscular hyoscine Nbutyl bromide combination in renal colic.
Due to low cost, ease of administration, and low adverse effects of desmopressin and hyoscine in comparison with morphine extracts and nonsteroid anti-inflammatory drugs, 1 this study was conducted to compare the analgesic effect of hyoscine N-butylbromide and desmopressin combination with hyoscine Nbutylbromide alone in patients with acute renal colic.

Methods
This open-labeled clinical trial had been approved by Ethics Committee of Lorestan University of Medical Sciences.Written informed consent was obtained from the patients or their relatives while they were being admitted.3]7 Patients who were 18 to 55 years old with clinically diagnosed acute renal colic and without pregnancy, addiction, and any history of hypertension, cardiac insufficiency, surgery on kidneys or ureters, receiving any analgesics/intravenous fluid therapy just before admission, and history of any drug reaction to hyosicne N-butylbromide at emergency ward of Shohada-e-Ashayer hospital (in Khorramabad city, the west of Iran) were randomly divided into two different treatment groups, using a simple randomization method.A shuffle deck of cards (n = 116) provided before the initiation of the study.Half of the cards labeled A (group A) and the other half labeled B (group B).For including a patient, a card was randomly taken from 116 shuffled cards.The taken cards were not returned back to the deck.As a result after inclusion of 116 patients in the study, 58 patients were randomly allocated to each treatment group.
A visual analog scale (VAS) score (scored from 0-10) at 0, 30, and 60 minutes of drug administration was utilized to assess the severity of patients' pain.In each time point, the emergency physician showed the printed VAS line to the patients and asked them to show the number represents their perception of their current pain.
During the study, if a patient could not bear the pain and did not want to continue as a study sample he/she was excluded and administered morphine.
Quantitative data was presented as mean ± standard error of mean (SEM).Repeated measurements ANOVA followed by Bonferroni's Post-hoc test, independent sample t test and chi-square tests were used in order to analyze the findings.

Results
The study included 116 patients randomly divided into two different groups (Table 1).Two patients did not continue the study, due to non-tolerable pain.
On admission, the mean pain level of patients in group A and B was 8.95 ± 0.11 and 8.95 ± 0.12, respectively (independent t test: p = 0.4).
After 30 minutes the pain decreased in 34 patients (60%) of group A and 49 patients (86%) of group B (chi square: p = 0.001).At this time the mean of pain level of patients in group A and B was 7.26 ± 0.25 and 5.95 ± 0.28, respectively (independent t test: p = 0.001).
In comparison with the time of admission and 30 minutes after it, at 60 minutes after drug administration all patients (100%) in group B revealed pain decreasing, however 11 patients (19%) in group A never showed any pain decreasing (chi square: p = 0.0004).At this time mean of pain levels in group A and B were equal to 6.80 ± 0.31 and 3.71 ± 0.31, respectively (independent t test: p = 0.001).
In both groups during one hour follow-up, there was a decrease in pain levels but in desmopressin plus hyoscine N-butylbromide group (group B) the trend of pain score decreasing kept its consistency, and after 60 minutes the pain score significantly was less than 30 minutes however in the hyoscine Nbutylbromide group (group A) the score at 60 minutes was not less than 30 minutes (repeated measurements ANOVA: group A: p = 0.07, group B: p = 0.005) (Figure 1).No patient showed any side effects.

Discussion
Patients with renal colic usually require immediate diagnosis and treatment. 2,4Both nonsteroidal anti-inflammatory drugs and morphine have routinely been used for pain control in patients with acute renal colic. 1,3,8Many side effects may arise from these drugs.Narcotic analgesics can induce adverse effects such as sedation, respiratory depression, constipa-tion, addiction, nausea, and vomiting.Moreover non-steroidal anti-inflammatory drugs (NSAIDs) are not harmless and safe in peptic ulcer disease, renal failure, or recent GI bleeding. 9In addition, NSAIDs can induce renal failure due to interstitial nephritis. 10Therefore, new agents with fewer side effects are of research interest.
Along with pain relieving agents, some physicians use diuretics besides hydration for patients with renal colic.This idea may traditionally arise from using hydration and diuretics to assist stone passage.But some experts concern about the increased hydrostatic fluid pressure in the obstructed urinary tract which can potentially exacerbate patients' pain. 1,9Increased hydrostatic pressure proximal to the stone and possible stone migration, increased ureteral peristalsis, tilting of the stone, and intermittent obstructions are the main reasons of pain exacerbation in over-hydrated patients. 1,3herefore, it seems that using antispasmodic agents in combination with drugs which minimize hydrostatic pressure of urinary system may be useful in patients with renal colic.Antimuscarinic drugs including hyoscine N-butylbromide are used for the treatment of smooth muscle spasm.In the genitourinary system the autonomic nervous system is involved in the regulation of ureteric activity by controlling smooth muscle contractility and peristalsis. 9,11A recent study showed that hyoscine N-butylbromide decreases human ureteric activity to some extent. 9Although antimuscarinic drugs are associated with several adverse effects such as photophobia, facial flushing, dry mouth and skin, loss of accommodation, urinary retention and urgency, and constipation 9 ; they seem to be safer than opium extracts or nonsteroidal antiinflammatory drugs.
In a study which compared effect of hyoscine N-butylbromide with placebo for patients with stone related renal colic, Holdgate et al demonstrated that hyoscine N-butylbromide does not reduce opioid requirements or the need for ongoing opioid analgesia. 5On the other hand some studies revealed that using antimuscarinics decreases pain compared to placebo. 6,12,13omparing mean intraureteral pressure in two groups of animals showed a significant reduction in pressure following an acute obstruction in subjects treated with desmopressin. 1,14Desmopressin possibly works by reducing the intraureteral pressure, but it may also directly relax the renal pelvic and ureteral musculature. 1,3A central analgesic effect through the release of hypothalamic betaendorphins has been proposed but remains unproved.But up to now the most proper mechanism has not recovered yet.It is not clear whether desmopressin affects renal function or it facilitates stone passage. 36][17] Moreover, desmopressin relieves pain quickly with no apparent side effect and reduces the need for other analgesic medications, and can be the only therapy necessary for some patients. 1Interestingly, in the present study 20 µg of intranasal desmopressin significantly decreased patients' pain.Therefore, compared to the previous studies which used 40 µg desmopressin, a good effect was observed.][17] The present study showed that hyosine Nbutylbromide either alone or in combination with desmopressin was effective in patients with renal colic.The analgesic effect of the combination was more significant.

Conclusions
Desmopressin in combination with hyoscine N-butylbromide appears to be a promising alternative or adjunct to analgesic medications in patients with acute renal colic, especially in patients in whom narcotics cannot be used.Further studies on different doses of desmopressin and the parameters which can possibly identify the subgroup of patients who respond better to this medication are needed.

Table 1 .
Features of patients with renal colic in study groups